Download MendeleyCrystal structure of the peptidyl-cysteine decarboxylase EpiD complexed with a pentapeptide substrate.
Blaesse, M., Kupke, T., Huber, R., Steinbacher, S.(2000) EMBO J 19: 6299-6310
- PubMed: 11101502
- DOI: https://doi.org/10.1093/emboj/19.23.6299
- Primary Citation of Related Structures:
1G5Q, 1G63 - PubMed Abstract:
Epidermin from Staphylococcus epidermidis T¨¹3298 is an antimicrobial peptide of the lantibiotic family that contains, amongst other unusual amino acids, S:-[(Z:)- 2-aminovinyl]-D-cysteine. This residue is introduced by post-translational modification of the ribosomally synthesized precursor EpiA. Modification starts with the oxidative decarboxylation of its C-terminal cysteine by the flavoprotein EpiD generating a reactive (Z:)-enethiol intermediate. We have determined the crystal structures of EpiD and EpiD H67N in complex with the substrate pentapeptide DSYTC at 2.5 A resolution. Rossmann-type monomers build up a dodecamer of 23 point symmetry with trimers disposed at the vertices of a tetrahedron. Oligomer formation is essential for binding of flavin mononucleotide and substrate, which is buried by an otherwise disordered substrate recognition clamp. A pocket for the tyrosine residue of the substrate peptide is formed by an induced fit mechanism. The substrate contacts flavin mononucleotide only via Cys-Sgamma, suggesting its oxidation as the initial step. A thioaldehyde intermediate could undergo spontaneous decarboxylation. The unusual substrate recognition mode and the type of chemical reaction performed provide insight into a novel family of flavoproteins.
Organizational Affiliation:
Abteilung f¨¹r Strukturforschung, Max-Planck-Institut f¨¹r Biochemie, Am Klopferspitz 18a, 82152, Germany.
